Similarities have been shown to exist between neurotensin (NT) and neuroleptics by other investigators. Intrinsic enkephalinergic neurons in striatum (ST) and in nucleus accumbens (NA) appear to be regulated transsynaptically raising the question whether a similar regulation is operative for NT containing neurons which are also present in these areas. Previous results indicated that in rat haloperidol injection can increase the NT selectively in NA and ST. The effect is observed either after acute or repeated treatment. We have now studied the NT content of various brain areas after treatment with different antipsychotic drugs. The results indicate that all the neuroleptics tested (chloropromazine 6.0 mg/kg; trifluoroperazine 2.0 mg/kg; pimozide 1.5 mg/kg; haloperidol 1 mg/kg) increase the content of NT in NA and ST. On the contrary promazine (10 mg/kg) and prometazine (25 mg/kg) which are structurally related to phenothiazines but with weak or no neuroleptic activity failed to increase the NT content of NA and ST. This effect is specific for NA and ST and it is not observed in preoptic area hypothalamus, septum, amygdala although these areas are enriched in NT. The neuroleptics induced increase of NT in NA and ST suggest a modulation of NT metabolism through dopaminergic synapses.